(1) Field of the Invention
The present invention relates to factor X zymogen compositions useful for inducing hemostasis. The compositions are generally substantially free of activators for the X zymogen.
(2) Prior Art
Clinical treatment of bleeding disorders arising from actual or apparent deficiencies of one or more clotting factors is commonly predicated upon a replacement therapy designed to correct the deficiency and restore the plasma concentration of the various clotting factors to that necessary to ensure adequate hemostasis.
Therapeutic materials employed in the management of bleeding disorders generally comprise plasma or plasma fractions of varying degrees of purity, typically plasma concentrates partially purified with respect to the deficient clotting factor or factors. Exemplary of such fractions are factor IX complex concentrates comprising major proportions of the vitamin K-dependent clotting factors factor II (prothrombin), factor VII, factor IX, factor X, protein C, and protein S. This concentrate, also referred to as factor IX concentrate, prothrombin complex concentrate (PCC), and prothrombin concentrate (PPSB), is used in replacement therapy for diseases associated with deficiencies of these factors, especially hemophilia B (Christmas disease), characterized by a congenital deficiency of factor IX. Surprisingly, however, factor IX concentrates, especially activated factor IX concentrates such as FEIBA and AUTOPLEX, have proved useful in the treatment of classic hemophilia with factor VIII immune inhibitor, and also in the treatment of other bleeding disorders with acquired immune inhibitors. These products also vary considerably in potency and manifestation of side effects on a clinical level. Owing to these anomalies, it has become of interest to elucidate the coagulation mechanisms involved in the therapeutic use of factor IX concentrates.
Coagulation activity of these concentrates in treating disorders other than deficiencies of the vitamin K-dependent clotting factors has been tentatively ascribed in the literature to the presence of various factors, such as factor VIII (Barrowcliffe, et al. Thrombosis Res. 21: 181-186, 1981), or a factor having "Xa-like activity" (Elsinger, Activated Prothrombin Complex Concentrates: Managing Hemophilia with factor VIII Inhibitor, Mariani, et al. eds. pp. 77-81, 1982). While a few parameters for the mechanism have been suggested, such as the involvement of factor V, reported results have been generally inconclusive.